Functional characterization of MdERF113 in apple.

The AP2/ERF family is an important class of transcription factors involved in plant growth and various biological processes. One of the AP2/ERF transcription factors, RAP2.6L, participates in various stresses responses. However, the function of RAP2.6L is largely unknown in apples (Malus domestica). In this study, an apple gene homologous to Arabidopsis AtRAP2.6L, MdERF113, was analyzed by bioinformatic characterization, gene expression analysis and subcellular localization assessment. MdERF113 was highly expressed in the sarcocarp and was responsive to hormonal signals and abiotic stresses. MdERF113-overexpression apple calli were less sensitive to low temperature, drought, salinity, and abscisic acid than wild-type. Subcellular localization revealed that MdERF113 was a nuclear-localized transcription factor, and yeast experiments confirmed that MdERF113 has no autonomous activation activity. Overall, this study indicated that MdERF113 plays a role in regulating plant growth under abiotic conditions.

A Zero-Dimensional Hybrid Cadmium Perovskite with Highly Efficient Orange-Red Light Emission.

Low-dimensional organic-inorganic hybrid metal halide materials have been extensively studied due to their excellent optoelectronic performances. Herein, by using the facile wet-chemistry method, we designed one new hybrid cadmium bromide of (H3AEP)2CdBr6·2Br based on discrete octahedral [CdBr6]4- units. Remarkably, the bulk crystal of (H3AEP)2CdBr6·2Br exhibits strong broadband orange-red light emission from the radiative recombination of self-trapped excitons (STEs) with a high photoluminescence quantum yield (PLQY) of 9%. Benefiting from the highly efficient luminescent performance, this 0D cadmium perovskite can be utilized as an excellent down-conversion red phosphor to assemble a white light-emitting diode, and a high color rendering index (CRI) of 93 is realized. As far as we know, this is the first orange-red light-emitting hybrid cadmium perovskite which promotes the full-color display in this system.

Study on the effect of municipal solid landfills on groundwater by combining the models of variable leakage rate, leachate concentration, and contaminant solute transport.

The landfill with low economic cost and technical barrier has become a popular option for municipal solid waste treatment, but it is likely to seriously pollute groundwater by solute leaching. In this study, the pollutants concentration model, leakage rate model, and the solute transport model were coupled to investigate the effect of municipal solid waste landfill on groundwater quality. Major results obtained are, (1) the leakage rate of leachate differs significantly among the landfilling stage, covering stage and completely covered stage as the leachate depth varies with the infiltration rainfall. The contact condition between HDPE and CCL was found to be a key factor in determining the leakage rate of leachate. Ensuring good connection between HPDE and CCL is thus critical in protecting groundwater from being polluted by landfill. (2) The NH3-N as a proxy for organic pollutants was generated via the degradation process, and Cl- as a proxy for inorganic pollutants is a leachable fraction of mobilized substances. The concentration of Cl- is higher than that of NH3-N before 7600 days, then the concentration of NH3-N becomes roughly stable while that of Cl- continues to decrease. (3) The load of NH3-N as a proxy for organic pollutants declines linearly downwards before the completely covering stage. The load of Cl- as a proxy for inorganic pollutants increased during the first five years, and then declined. (4) In the case study, the path of maximum pollutants concentration is perpendicular to the groundwater contour, and the maximum pollutants concentration has two peaks, occurring on 7106 days and 11,554 days, respectively. The change laws of maximum pollutants concentration are similar for different connections between HPDE and CCL.

Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.

BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR). In this study, we focused on the correlations between O-GlcNAcylation and STAT3 phosphorylation, and their potential effects with regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3 were detected in DR-affected tissues and primary RVECs. The relationship between O-GlcNAcylation and STAT3 was further delineated by immunoprecipitation and Western blot analysis. Effects of O-GlcNAcylation on human RVEC apoptosis and involved protein expression were assayed with flow cytometry and Western blot. RESULTS: Global O-GlcNAcylation and pSTAT3 levels were significantly elevated in diabetic rat retina and primary RVECs under high glucose conditions. In vitro assays demonstrated that the Tyr705 site was sensitive to high glucose. While O-GlcNAcylation inhibited p727STAT3 expression, augmented O-GlcNAcylation could balance p705STAT3 expression within relatively high levels corresponding to vascular endothelial growth factor (VEGF) changes. Immunoprecipitation revealed that STAT3 was modified by O-GlcNAcylation and phosphorylation simultaneously. Next, we observed that overexpression of O-GlcNAcylation could relieve human RVEC apoptosis related to the JAK2-Tyr705STAT3-VEGF pathway. CONCLUSION: O-GlcNAcylation could relieve RVECs apoptosis through the STAT3 pathway in DR, and O-GlcNAcylation combined with STAT3 phosphorylation might open up new insights into the mechanisms of DR and other diabetic complications.

Assembly of Multifold Helical Polyoxometalate-Based Metal-Organic Frameworks as Anode Materials in Lithium-Ion Batteries.

For exploring the multifold helical fabrication of polyoxometalate (POM)-based hybrid compounds, four POM-based crystalline compounds with different meso-helices, H3[Ag27(trz)16(H2O)6][SiW12O40]2·5H2O (1), H[Ag27(trz)16(H2O)4][PW12O40]2·2H2O (2), [Ag23(trz)14(H2O)2][HSiW12O40] (3), and [Ag23(trz)14(H2O)2][PW12O40] (4), were successfully isolated by using the delicate 1,2,3-triazole ligand and silver ions in this work. Crystal analysis reveals that compounds 1 and 2 and compounds 3 and 4 are isomorphous and display 2-/4-fold mixed meso-helices and simple 2-fold meso-helices, respectively. In addition, due to the reversible multielectron redox behavior and electron storage functions of POMs, compounds 1 and 3 were studied as anode materials in lithium-ion batteries (LIBs). Compounds 1 and 3 show very high lithiation capacities (1356 and 1140 mAh g-1, respectively) in the initial cycle, which are much higher than those of (NBu4)4[SiW12O40] and commercial graphite at the current density of 100 mA g-1. More importantly, both compounds also show good stable performance after 100 cycles.

Central nervous system progression in advanced non-small cell lung cancer patients with EGFR mutations in response to first-line treatment with two EGFR-TKIs, gefitinib and erlotinib: a comparative study.

BACKGROUND: Central nervous system (CNS) brain metastasis of advanced non-small cell lung cancer (NSCLC) patients confers a worse quality of life and prognosis. The efficacy comparison of two first-generation epidermal growth factor receptor (EGFR) inhibitors erlotinib or gefitinib as first-line treatment for CNS metastasis NSCLC patients with EGFR-sensitizing mutations is yet to be elucidated. METHODS: A retrospective analysis was done on cerebral metastasis rate after erlotinib or gefitinib as first-line treatment for advanced NSCLC patients with EGFR-sensitizing mutations. Time to neurological progression (nTTP) and median progression-free survival (mPFS) were calculated. RESULTS: The study involved 279 patients (erlotinib group: 108, gefitinib group: 171). After a median follow-up of 22 months, 27 patients (25%) in the erlotinib group and 60 patients (35.1%) in the gefitinib group showed CNS progression. The HR of CNS progression for erlotinib versus gefitinib was 0.695 [95% confidence interval (CI), 0.406-1.190], suggesting a risk reduction of 30.5% although not achieving statistical significance. The 6-, 12- and 18-month cumulative CNS progression rates were 0.9, 3.7 and 12% for erlotinib compared with corresponding rates of 5.8, 9.4 and 17% for gefitinib (P = 0.181). However, for those patients with preexisting brain metastases prior to EGFR-TKI treatment, erlotinib as first line treatment significantly extended the median nTTP in comparison to gefitinib (30 months vs 15.8 months, p = 0.024). CONCLUSIONS: Our data show that nTTP can be effectively extended in preexisting brain metastases patients with EGFR-sensitizing mutations initially treated with erlotinib compared with gefitinib. If confirmed, our results indicate that erlotinib may play an important role in controlling CNS progression from EGFR mutation-positive NSCLC.

[Non-Invasive Detection of Blood Glucose Concentration Based on Photoacoustic Spectroscopy Combined with Principle Component Regression Method].

This paper presents a photoacoustic noninvasive setup of detecting blood glucose based on the tunable pulsed laser coupled with the confocal ultrasonic transducer and the forward detection model. To validate the reliability of the setup, in the experiments, the different concentrations of glucose aqueous solution are excitated by the Q-switched 532 nm pumped Nd∶YAG pulsed laser to generate the time-resolved photoacoustic signals. And the glucose aqueous solutions are scanned by the tunable pulsed laser in the infrared waveband from 1 300 to 2 300 nm with the interval of 10nm and the photoacoustic peak-to-peak values are gotten. The difference spectral method is used to get the characteristic wavelengths of glucose, and the principle component regression algorithm is used to determine three optimal wavelengths and establish the correction mathematical model between the photoacoustic peak-to-peak values and the concentrations. The experimental results demonstrate that the mechanism of the photoacoustic signal is agreement with the cylindrical model, and the predicted results of the correction and prediction samples based on the established correction model demonstrate that the root-mean-square error of correction and prediction are all less than 10 mg·dl-1, the correlation coefficient reaches 0.993 6.

Clinical and radiological outcomes following arthroscopic-assisted management of tibial plateau fractures: a systematic review.

PURPOSE: To carry out a systematic review of the literature on arthroscopic-assisted management (all types) of tibial plateau fractures to gain a more comprehensive understanding of clinical outcomes with this surgical technique, specifically to determine whether this may be a viable technique for the management of tibial plateau fractures. METHODS: MEDLINE, Cochrane, and EMBASE databases were searched until July 2013 using combinations of the search terms: tibial plateau, fractures, and arthroscopically/arthroscopic/arthroscopy/percutaneous/minimally invasive. Inclusion criteria were observational study, patients with tibial plateau fractures, and clinical and radiological outcomes assessed using Rasmussen scoring system. The outcome measures of interest were clinical and radiological Rasmussen scores and the prevalence of secondary osteoarthritis. RESULTS: A total of 12 studies, 5 prospective and 7 retrospective, involving 353 patients were included in the review. The majority of patients in most studies had Schatzker type I-III fractures. The graft material used varied between studies. The length of the follow-up was typically between 34 and 38 months. Mean clinical Rasmussen scores ranged from 25.5 to 28.4. In each study, the majority (≥80 %) of patients had excellent/good clinical Rasmussen scores. In each study, the majority (≥63 %) of patients had excellent/good radiological Rasmussen scores. The proportion of patients who experienced secondary osteoarthritis was variable, ranging from 0 to 47.6 %. CONCLUSIONS: The results of this systematic review indicate that arthroscopic-assisted management of tibial plateau fractures can be effective. Surgeons should consider using this approach when treating patients with tibial plateau fractures. LEVEL OF EVIDENCE: III.

An extended anterolateral approach for posterolateral tibial plateau fractures.

PURPOSE: The best approach for treating posterolateral tibial plateau fractures remains controversial. The clinical results of an extended anterolateral approach on such fractures are discussed in this study. METHODS: Between 2010 and 2011, ten patients with posterolateral tibial plateau fracture were treated using an extended anterolateral approach with a proximal tibial locking compression plate. The epidemiological data, operation details, and clinical outcomes over 26.4 ± 2.3 months (range 24-30 months) of follow-up were prospectively collected and analyzed. RESULTS: The average surgical duration was 91.5 ± 18.7 min (range 80-130 min). An anatomic reduction rate of 90 % (9/10) was observed although one patient with a lateral comminuted fracture and dislocation presented a 2-mm joint surface depression postoperatively. The average fracture healing time was 10.6 ± 1.8 weeks (range 8-14 weeks), with an average hospital for special surgery knee score of 95.3 ± 6.5 points (range 80-100 points), an average knee flexion of 119.8° ± 17.2° (range 95°-140°) and an average knee extension of 2.1° ± 2.1° (range 0°-6°). No complications were found. CONCLUSIONS: The extended anterolateral approach with a proximal tibial compression plate offers direct and complete surgical exposure and may provide an effective method for the surgical treatment of posterolateral tibial plateau fractures. LEVEL OF EVIDENCE: Therapeutic, Level IV.

Rapid and high-throughput identification of recombinant bacteria with mass spectrometry assay.

OBJECTIVE: To construct a rapid and high-throughput assay for identifying recombinant bacteria based on mass spectrometry. METHODS: Matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) techniques were used to identify 12 recombinant proteins (10 of Yersinia pestis, 1 of Campylobacter jejuni and 1 of Helicobacter pylori). A classification model for the various phase of recombinant bacteria was established, optimized and validated, using MALDI-TOF MS-ClinProTools system. The differences in the peptide mass spectra were analyzed by using Biotyper and FlexAnalysis softwares. RESULTS: Models of GA, SNN, and QC were established. After optimizing the parameters, the GA recognition model showed good classification capabilities: RC=100%, mean CVA=98.7% (the CVA was 96.4% in phase 1, 100% in phase 2, 98.4% in phase 3, and 100% in phase 4, respectively) and PPV=95%. This model can be used to classify the bacteria and their recombinant, which only requires 3.7×103 cells for analysis. The total time needed is only 10 min from protein extraction to reporting the result for one sample. Furthermore, this assay can automatically detect and test 96 samples concurrently. A total of 48 specific peaks (9, 16, 9, and 14 for the four stages, respectively) was found in the various phase of recombinant bacteria. CONCLUSION: MALDI-TOF MS can be used as a fast, accurate, and high-throughput method to identify recombinant bacteria, which provide a new ideas not only for recombinant bacteria but also for the identification of mutant strains and bioterrorism pathogens.

MdSnRK1.1 interacts with MdGLK1 to regulate abscisic acid-mediated chlorophyll accumulation in apple.

Abscisic acid (ABA), as a plant hormone, plays a positive role in leaf chlorosis; however, the underlying molecular mechanism is less known. Our findings provide ABA treatment reduced the chlorophyll accumulation in apple, and Malus × domestica Sucrose Non-fermenting 1-Related Protein Kinase 1.1 (MdSnRK1.1) participates in the process. MdSnRK1.1 interacts with MdGLK1, a GOLDEN2-like transcription factor that orchestrates development of the chloroplast. Furthermore, MdSnRK1.1 affects MdGLK1 protein stability through phosphorylation. We found that Ser468 of MdGLK1 is target site of MdSnRK1.1 phosphorylation. MdSnRK1.1-mediated phosphorylation was critical for MdGLK1 binding to the target gene MdHEMA1 promoters. Collectively, our results demonstrate that ABA activates MdSnRK1.1 to degrade MdGLK1 and inhibit the accumulation of chlorophyll. These findings extend our understanding on how MdSnRK1.1 balances normal growth and hormone response.

Aspertaichamide a, a novel cytotoxic prenylated indole alkaloid possessing a bicyclo[2.2.2]diazaoctane framework from a marine algal-derived endophytic fungus aspergillus taichungensis 299.

Filamentous fungi belonging to the genus Aspergillus are prodigious producers of alkaloids, particularly prenylated indole alkaloids, that often exhibit structurally diversified skeletons and potent biological activities. In this study, five prenylated indole alkaloids possessing a bicyclo[2.2.2]diazaoctane core ring system, including a novel derivative, namely aspertaichamide A (1), as well as four known compounds, (+)-stephacidin A (2), sclerotiamide (3), (-)-versicolamide B (4), and (+)-versicolamide B (5), were isolated and identified from A. taichungensis 299, an endophytic fungus obtained from the marine red alga Gelidium amansii. The chemical structures of the compounds were elucidated by comprehensive NMR and HRESIMS spectroscopic analyses. In addition to the previously reported prenylated indole alkaloids, aspertaichamide A (1) was characterized as having an unusual ring structure with the fusion of a 3-pyrrolidone dimethylbenzopyran to the bicyclo[2.2.2]diazaoctane moiety, which was rare in these kinds of compounds. The absolute configuration of 1 was determined by TDDFT-ECD calculations. In vitro cytotoxic assays revealed that the novel compound 1 possessed selective cytotoxic activity against five human tumor cell lines (A549, HeLa, HepG2, HCT-116, and AGS), with IC50 values of 1.7-48.5 µM. Most importantly, compound 1 decreased the viability of AGS cells in a concentration-dependent manner with an IC50 value of 1.7 µM. Further studies indicated that 1 may induce AGS cells programmed cell death via the apoptotic pathway.

Brassinosteroids biosynthetic gene MdBR6OX2 regulates salt stress tolerance in both apple and Arabidopsis.

Salt stress is a critical limiting factor for fruit yield and quality of apples. Brassinosteroids (BRs) play an important role in response to abiotic stresses. In the present study, application of 2,4- Epicastasterone on seedlings of Malus 'M9T337' and Malus domestica 'Gala3' alleviated the physiological effects, such as growth inhibition and leaf yellowing, induced by salt stress. Further analysis revealed that treatment with NaCl induced expression of genes involved in BR biosynthesis in 'M9T337' and 'Gala3'. Among which, the expression of BR biosynthetic gene MdBR6OX2 showed a three-fold upregulation upon salt treatment, suggesting its potential role in response to salt stress in apple. MdBR6OX2, belonging to the CYP450 family, contains a signal peptide region and a P450 domain. Expression patterns analysis showed that the expression of MdBR6OX2 can be significantly induced by different abiotic stresses. Overexpressing MdBR6OX2 enhanced the tolerance of apple callis to salt stress, and the contents of endogenous BR-related compounds, such as Typhastero (TY), Castasterone (CS) and Brassinolide (BL) were significantly increased in transgenic calli compared with that of wild-type. Extopic expression of MdBR6OX2 enhanced tolerance to salt stress in Arabidopsis. Genes associated with salt stress were significantly up-regulated, and the contents of BR-related compounds were significantly elevated under salt stress. Our data revealed that BR-biosynthetic gene MdBR6OX2 positively regulates salt stress tolerance in both apple calli and Arabidopsis.

Association of CFH and CFB gene polymorphisms with retinopathy in type 2 diabetic patients.

OBJECTIVES: The complement system is a key component of innate immunity and has been implicated in the pathogenesis of diabetic retinopathy (DR). This study aimed at investigating whether polymorphisms of two genes in the complement pathway, complement factor H (CFH) and complement factor B (CFB), are associated with DR. METHODS: 552 well-defined subjects with type 2 diabetes, consisting of 277 DR patients and 275 diabetic controls, were recruited. Four Tag-SNPs rs1048709, rs537160, rs4151657, and rs2072633 in CFB and rs800292 (I62V) in CFH were examined using TaqMan Genotyping Assays. RESULTS: There were significant increases in the frequencies of A allele and AA genotype for rs1048709 in DR patients compared with diabetic controls (P(corr) = 0.035, OR = 1.42; P(corr) = 0.02, OR = 2.27, resp.): meanwhile, significant decreases in the frequencies of A allele and AA genotype for rs800292 were observed in DR patients compared with diabetic controls (P(corr) = 0.04, OR = 0.72; P(corr) = 0.015, OR = 0.51, resp.). Joint effect of these two loci was also identified. Moreover, rs800292/AA genotype was found to be related with delayed progression to DR. CONCLUSIONS: CFH-rs800292 and CFB-rs1048709 are associated with the presence of DR, which strengthens the concept that complement system plays an important role in the pathogenesis of DR.

Operative versus non-operative treatment for clavicle fracture: a meta-analysis.

PURPOSE: The purpose of this study was to assess the effects of operative and non-operative treatment on clavicle fractures. METHOD: Relevant clinical trials on the operative and non-operative treatment for clavicle fractures were retrieved through searching the databases MEDLINE, Embase, OVID and the Cochrane Central Register of Controlled Trials up to December 2011. The quality of the included studies was assessed by two authors. A meta-analysis was carried out on homogeneous studies. Five studies involving 633 clavicle fractures were included. RESULTS: The differences in nonunion [risk ratio (RR) 0.12, 95 % confidence interval (CI) 0.05-0.29], malunion (RR 0.11, 95 % CI 0.04-0.29) and neurological complications (RR 0.45, 95 % CI 0.25-0.81) were statistically significant between operative and non-operative treatment. There was no statistically significant difference in delayed union (RR 0.78, 95 % CI 0.31-1.95). CONCLUSION: Operative treatment is better than non-operative treatment, but decisions should be made in accordance with specific conditions for clinical application.

[Development of spectrometer for tongue diagnosis based on plane holography concave grating].

The traditional tongue inspection method should be urgently improved due to the relative large diagnosis error probability caused by the excessive dependence on the Chinese physician's experience and judgment. But the application of tongue diagnosis based on image processing is limited by some factors including the performance of light source, image acquisition device and the low recognition rate of similar color for different diseases. In order to overcome these drawbacks, the spectroscopy method was employed to analyze the tongue by using the unique fingerprint effect of tongue spectrum. A spectrometer for tongue diagnosis (STD) was developed to achieve this goal in this paper. Meanwhile, to overcome the shortcomings of traditional light-splitting devices, a plane holographic concave grating was used as the diffractive grating, which not only can improve the luminous flux efficiency and miniaturize system, but also improve the spectral imaging quality and resolution. Experimental results demonstrated that the spectral range of STD reached 340-850 nm, and its spectral resolution is better than 2 nm. And the result of simulation experiment validated the feasibility of spectrometer's system.

Expression of CD26 and CXCR4 in prostate carcinoma and its relationship with clinical parameters.

BACKGROUND: Prostate cancer is one of the most common cancer types both in western and eastern countries, involving mostly elder men. The mechanisms underlying the prostate cancer development remain unclear. Prostate-specific antigen (PSA) is the only well accepted marker for prostate cancer diagnosis and prognosis. The diagnosis and treatment of prostate cancer are facing big challenges. Here, we evaluated the expression of Dipeptidyl peptidase IV (CD26/DPPIV) and C-X-C chemokine receptor type 4 (CXCR4), two known cancer-related molecules but without clear data on prostate cancer population, and their correlation with clinical parameters in prostate cancer tissue array. To explore the correlation of CD26 and CXCR4 expression in prostate carcinoma and their relationship with clinical parameters. MATERIALS AND METHODS: We immunohistochemically stained the tissue array containing samples from 36 cases with prostate cancer with CD26 and CXCR4 antibodies. Then we analyzed the expression of CD26 and CXCR4 and its relationship with clinical parameters. We used immunohistochemical staining to evaluate the expression of CD26 and CXCR4 in a set of tissue array containing 36 cases of prostate cancers and eight peritumoral normal prostatic tissues. The data were statistically analyzed with Statistical Package for Social Sciences (SPSS) 16.0 software. The difference between parameters was compared with nonparametric test and correlation analysis was performed with Spearman test. P < 0.05 was considered as significant. RESULTS: We found both CD26 and CXCR4 expression were higher in cancer tissue than in normal tissues. CD26 and CXCR4 levels were correlated with each other. Moreover, CD26 was correlated with PSA level, tumor residue, cancer stage, and tumor size in the studied samples. CONCLUSION: Our data indicate that CD26 may be a good indicator for cancer behaviors of prostate cancer in clinic.

An apple NITRATE REDUCTASE 2 gene positively regulates nitrogen utilization and abiotic stress tolerance in Arabidopsis and apple callus.

Nitrogen (N) is an essential element that plays an important role in crop biomass accumulation and quality formation. Increased crop yield is relied on excessive application of fertilizers, which usually leads to environmental pollution and unsustainable development. Thus, identification and characterization of genes involved in promoting nitrogen use efficiency is of high priority in crop breeding. The activity of nitrate reductase (NR) plays a critical role in nitrogen metabolism. In model plant Arabidopsis, NITRATE REDUCTASE 2 (NIA2), one of the two NRs, is responsible for about 90% of the NR activity. In this study, MdNIA2 gene in apple (Malus domestica) genome was screened out and identified by using AtNIA2 as bait. Phylogenetic analysis revealed that MdNIA2 had the closest evolutionary relationship with MbNIA from Malus baccata. Ectopic expression of MdNIA2 in Arabidopsis elevated the nitrogen use efficiency and increased root hair elongation and formation, resulting in promoted plant growth. Furthermore, the overexpression of MdNIA2 improved salt and drought tolerance in transgenic Arabidopsis and improved the salt tolerance of transgenic apple callus, and MdNIA2-reagualted NO metabolism might contribute to the abiotic stress tolerance. Overall, our data indicate the critical role of MdNIA2 in regulating nitrogen utilization efficiency and abiotic stress responses.

Gastrocnemius-derived BDNF promotes motor function recovery in spinal cord transected rats.

This study evaluated the role of gastrocnemius-derived brain-derived neurotrophic factor (BDNF) and possible mechanism in motor improvement in T10 spinal cord transection (SCT) rats. There was complete paralysis in hindlimbs immediately after SCT, followed by partial functional restoration with time going. The level of BDNF but not its mRNA gradually increased in caudal stump after SCT, whereas a significant increase in both BDNF and its mRNA was simultaneously seen in gastrocnemius. Injection of BDNF antibody into the gastrocnemius significantly decreased hindlimb locomotor function, downregulated the level of BDNF and its mRNA together with extracellular signal-regulated kinase 1/2 (Erk1/2). Moreover, ventral root ligation led to decrease both BDNF and Erk in caudal stump, indicating BDNF transportation from gastrocnemius into the spinal cord. We concluded that gastrocnemius-derived BDNF reduced motor functional deficits in SCT rats through Erk signaling pathway. These novel findings suggested the usage of BDNF in muscle for the treatment of spinal cord injury in clinic.

Immunological tolerance of human hepatocyte xenograft induced by adenovirus vector-mediated CTLA4Ig gene transfer.

BACKGROUND: Systemic administration of CTLA4Ig has been applied in inducing immunological tolerance of hepatocyte implants, but has potential for systemic immune inhibition. This study was designed to induce hepatocyte immunological tolerance by locally expressing CTLA4Ig in an attempt to improve the effectiveness of cell transplantation. METHODS: A normal human liver cell line (L02) was transfected with adenovirus vector containing the CTLA4Ig gene (Ad-CTLA4Ig-EGFP) in vitro, and the expression of CTLA4Ig by transfected cells was assessed by fluorescent imaging and immunocytochemical staining. Transfected cells then were injected into the spleen of Sprague-Dawley rats, the survival of cells was determined by immunohistochemistry, and the immune status was examined through CD4+ and CD69+ T cell-counts and ELISA detection of IL-2 in peripheral blood. RESULTS: L02 cells expressed CTLA4Ig in the cytoplasm for >4 weeks. Surviving L02 cells were observed in the experimental group at 3 and 4 weeks post-transplantation, while none was detected in the control group. Furthermore, the percentages of CD4+ and CD4+CD69+ T cells in the CTLA4-transfected group were 24.5% and 45.1%, markedly lower than those in the control group at 4 weeks post-transplantation (P<0.01). Furthermore, the IL-2 level was also lower in the CTLA4-transfected group than in the control group. CONCLUSION: Adenovirus-mediated CTLA4Ig gene transfer into human hepatocytes has the potential to become an effective method of inducing immunological tolerance in hepatocyte transplantation.